Antineoplastic effects and mechanisms of micheliolide in acute myelogenous leukemia stem cells
Abstract
Leukemic stem cells (LSCs) play a critical role in the onset, relapse, and resistance to multiple drugs in leukemia. Current treatments, such as conventional chemotherapy, primarily target the rapidly dividing leukemic cells and the cell cycle but are often ineffective against LSCs. Despite their low abundance in the bone marrow, LSCs can self-renew and replenish the differentiated malignant cells. Micheliolide (MCL), a natural guaianolide sesquiterpene lactone (GSL) found in Michelia compressa and Michelia champaca plants, has been shown to selectively induce cytotoxicity in CD34+CD38- LSCs. In this study, we demonstrate that DMAMCL significantly extends the lifespan of a mouse model of human acute myelogenous leukemia (AML). Mechanistic studies revealed that MCL induces its cytotoxic effects by inhibiting NF-κB expression and activity while generating reactive oxygen species (ROS) within the cells. These findings provide valuable insights into the mechanisms behind MCL-induced LSC cytotoxicity and encourage further preclinical research into MCL-based therapies for AML treatment.